Ganglioside expression in tissues of mice lacking the tumor necrosis factor receptor 1

This study presents a comparative analysis of gangliosides from lymphoid (s pleen and thymus) and other tissues (brain, liver, lung, muscle) of C57BL/6 mice homozygous (-/-) and heterozygous (+/-) for the tumor necrosis factor receptor 1 (TNFRp55). Quantitative and qualitative differences in the expr ession of the lipid-bound N-acetylneuraminic (Neu5Ac) and N-glycolylneurami nic acid (Neu5Gc) and of various ganglioside biosynthesis pathways were det ected between the tissues of the TNFRp55 -/- and the control TNFRp55 +/- mi ce. Sialic acid profiles showed a strong decrease in the absolute amount of sialic acids (Neu5Ac + Neu5Gc) in the lungs and thymus of homozygous (1.41 and 0.3 ng/mg wet weight, respectively) compared with control heterozygous animals (7.18 and 2.05 ng/mg wet weight, respectively). Considerable diffe rences of NeuSAc/NeuSGc ratios in the lungs, muscle, spleen, and thymus wer e also detected. The gangliosides G(M3)(Neu5Ac) and G(M3)(Neu5Gc) were the dominant gangliosides in the lungs of the control animals, whereas the knoc kout mice almost completely lacked these structures in this organ. Reduced expression of G(M1b)-type gangliosides (G(M1b) and GalNAc-G(M1b)) was also found in the lungs, spleen, and thymus of the TNFRp55 knockout mice. On the other hand, neolacto-series gangliosides were more abundant in the lungs, brain, and muscle of the knockout mice, whereas their expression in the liv er, spleen, and thymus was similar in both groups of animals. This study pr ovides in vivo evidence that TNF signaling via the TNFRp55 is involved in t he acquisition of a distinct ganglioside assembly in different mouse organs . TNFRp55 signaling seems to be especially important for the activation of the G(M1b)-type ganglioside biosynthetic pathway that is a unique character istic of the mouse lymphoid tissues. (C) 1999 Elsevier Science Ltd. All rig hts reserved.